Effects of a novel compound MCI-225 on impaired learning and memory in rats.

Abstract Effects of MCI-225, [4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride] on experimental amnesia were studied in rats and compared with those of THA [9-amino-1,2,3,4-tetrahydroacridine]. In the Morris-type water maze task, MCI-225 (1–10 mg/kg, PO) reduced the spatial learning impairment induced by scopolamine (0.5 mg/kg, IP). In a passive avoidance (PA) task, administration of MCI-225 prior to training (1–30 mg/kg, PO) lessened the carbon dioxide (CO 2 )-induced amnesia in a dose-dependent manner. MCI-225 (1–100 mg/kg) did not affect gross behavior. THA (0.1–3 mg/kg, PO) reduced scopolamine-induced learning deficits in the water maze task, but the effect was not significant. THA (0.3–3 mg/kg, PO) also ameliorated the CO 2 -induced amnesia, although slightly, in the PA task. THA (10 mg/kg, PO) increased locomotor activity and higher dose of THA (30 mg/kg, PO) induced tremor, hypersalivation, and muscle relaxation. These results suggest that MCI-225 lessens impairments in learning and memory without causing serious behavioral abnormalities.